Summary

Whole genome or whole exome sequencing tests are used to look for a genetic cause in newborns and children who have global developmental delay, intellectual disability or congenital anomalies –changes that are present from birth – when the cause is not apparent from the clinical findings or other testing. DNA sequencing is also used for the diagnosis of childhood cancer.

Why get tested?

Whole genome and whole exome sequencing are tests that look for changes in the genetic code that may be able to explain a child’s symptoms.  They are based on new technology that allows the rapid sequencing of large amounts of DNA. 
DNA sequencing determines the order of the DNA building blocks in a person’s genetic code. In whole genome and whole exome sequencing the building blocks that make up the DNA code are read and compared with a reference sequence. If differences are detected, they are investigated to see if they are a possible cause of the child’s clinical condition.

Whole genome sequencing (WGS)
Whole genome sequencing is a test that reads all the building blocks of a person’s DNA to try to determine if there are variants in genes that could be responsible for their clinical condition.

Whole exome sequencing (WES)
Whole exome sequencing is a test that can be performed instead of whole genome sequencing. It looks only at the genes that code for proteins in DNA and the remaining non-coding DNA sequences are not investigated. The coding regions are about one to two percent of the entire human genome. This test is done if the doctor thinks the cause of the clinical condition will be found using whole exome sequencing as it is faster to perform than whole genome sequencing and does not cost as much.

Having the test

Sample 
Whole genome and whole exome sequencing tests are usually performed on a blood sample. Where it is technically difficult to obtain a blood sample, such as in children with severe autism or young babies, a saliva sample can be used, however the failure rate is higher, and it needs to be arranged with the laboratory before sample collection.

Any preparation?
None

Your results

Our DNA is made up of chemical units called nucleotide bases. There are four different types and each have been given a letter – A,T,G and C. This is called the genetic alphabet.

Benign changes 
Each letter in the genome is compared with the reference sequence.  For all of us there are many thousands of differences between our DNA sequence and the reference sequence. These changes are known as variants, and they mostly do not cause any problem and are termed benign changes. 

Pathogenic variants 
Sometimes a variant is found in a gene that is known to cause the condition in the child and these are called pathogenic variants.  Finding such a variant will usually be sufficient for the child to be given a diagnosis and for the doctors to develop a treatment and management plan.  Understanding the cause of the condition can provide important information on how other children in the family may be affected.

Probably pathogenic 
Sometimes a gene variant is found that looks likely to be damaging, but there is not enough evidence available to know for certain that it is the cause the condition in the child.  These variants are reported as probably pathogenic.

Variants of uncertain significance (VUS)
Many gene variants are found, and the clinical significance of the change is not known. These variants are called variants of uncertain significance (VUS). As our knowledge of these gene variants improves over time, it may be possible to reclassify them as benign if they are found in healthy individuals, or clearly pathogenic, if they are found to be associated with certain conditions. 
 

Trio studies
To help clarify if a VUS may be the cause of the child’s condition, it can be helpful to see if the same variant is present in either of the parents. This is called trio studies.  If a healthy parent also has the same VUS as the child, it is unlikely to be the cause of the child’s condition.  If neither parent has the VUS then it is a new variant – known as a de-novo variant – and it could be the cause.
Even after looking at all the building blocks in all genes the cause of the child’s condition may not be found. Whole genome and whole exome sequencing tests are most powerful for the diagnosis of monogenic conditions – problems caused by a pathogenic variant in just one gene. However, for some children there may be more than one gene involved or the condition may not be genetic in origin.

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms.   It is important that you tell them everything you think might help. 

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely. 

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

Any more to know?

Generally, a genetic test result is available within two months. Whole genome or whole exome sequencing are covered by Medicare for a child under 10 who has dysmorphic facial appearance and one or more major structural congenital anomalies, or intellectual disability or global developmental delay of at least moderate severity to be determined by a specialist paediatrician. The test can only be ordered by a clinical geneticist or consultant physician plasticising as a specialist paediatrician, following consultation with a clinical geneticist.

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed. Get further trustworthy health information and advice from healthdirect.